Deletion of UTX, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.. Homo sapiens

Kabuki syndrome (KS) is a rare multiple congenital anomalies/mental retardation (MCA/MR) syndrome described in 19811,2. In 2010, exome sequencing identified MLL2 mutations in patients with KS3. Since then, 5 studies identified a mutation in MLL2 in 56-75,6% of KS patients3-7. Here, we describe 2 KS and 1 KS-like patient with a de novo partial or complete deletion of UTX, a histone demethylase interacting with MLL2 in gene regulation. UTX locates on the X chromosome and we showed that the X chromosome with the deleted copy of UTX is preferentially inactivated despite the fact that UTX escapes X-inactivation. This study unveiled deletion of UTX as a second cause of KS and highlights the growing role of histone methylase/demethylase in MCA/MR syndrome. Overall design: Two patients were analysed by Agilent array CGH 244K (AMADID: 014693) Three patients DNA were analyzed by CGH on custom targeted array 44K (AMADID: 032482). Two of them were initially analyzed using 244K Whole genome Arrays (AMADID: 014693). One third patient was selected given suspicion of deletion in one of the targeted gene (KDM6A) as amplification of some exons performed in our lab to sequence this gene failed.